卡维地洛对压力超负荷大鼠肥厚心肌线粒体呼吸功能的影响及其机制

Effect of carvedilol on mitochondrial respiratory function of pressure overload induced left ventricular hypertrophy in rats and its mechanism

目的:观察腹主动脉缩窄术后左心室肥厚大鼠心肌线粒体氧化呼吸功能的改变及卡维地洛的作用,探讨卡维地洛对压力超负荷心肌线粒体能量代谢的影响及机制。方法:用卡维地洛治疗腹主动脉缩窄术后的成年雄性SD大鼠,5周及15周后观察假手术组、腹主动脉缩窄组及卡维地洛治疗组大鼠血流动力学参数、心室重塑指标,常规石蜡切片观察心肌纤维结构;高速离心密度梯度法分离大鼠心肌线粒体,C lark氧电极法测定线粒体呼吸活性。结果:与对照组相比,腹主动脉缩窄组5周出现左心室肥厚,15周进一步加重,卡维地洛可减轻左心室肥厚;腹主动脉缩窄组5周Ⅲ态、Ⅳ态呼吸及氧化磷酸化效率(OPR)均增高,呼吸控制率(RCR)降低,卡维地洛可降低Ⅲ态、Ⅳ态呼吸及OPR,增高RCR;腹主动脉缩窄组15周Ⅲ态呼吸、RCR、OPR均降低,Ⅳ态呼吸无显著差异。应用卡维地洛后,与腹主动脉缩窄组15周比较,Ⅲ态呼吸、RCR、OPR增高,基本恢复至对照水平。各组间磷氧比均无显著差异。结论:肥厚心肌线粒体呼吸功能发生改变,卡维地洛可保护线粒体呼吸功能,从而改善心肌能量代谢,卡维地洛维持心肌正常能量代谢可能是其保护心肌作用的机制之一。

Objective： To understand the effect of Carvedilol on mitochondrial oxidative phosphorylation function during the development of pressure overload induced left ventricular hypertrophy in rats and its mechanism Methods ： Male SD rats were randomized into 6 groups ： 5- and 15-week coarctation of the abdominal aorta （H5, H15 ）, 5- and 15-week Carvedilol intervention （HR5, HR15 ） and 5- and 15-week sham operation （S5, S15）. Hemodynamics and ventricular remodeling parameters were measured, and the mitochondrial respiratory function was detected by Clark oxygen electrode three parameters and restored them to the level of the S15. Results ： Compared with Conclusion ： Mitochondrial respiratory function decreased during the development of pressure overload induced left ventricular hypertrophy in rats. Carvedilol could protect mitochondrial respiratory function and improve myocardial energy metabotism, which might be a mechanism underlying its protective effect on myocardium.